This proposal is a collaboration of multidisciplinary fields of peripheral nerve repair and regeneration, involving Collagen Matrix, Inc., leading the BRP, specializing in extracellular matrix design and engineering; Eastern Virginia Medical School, specializing in neuroscience and neurosurgery; Duke University specializing in neuroscience, entubulation repair of peripheral nerve, clinical neurology and urology; and University of . South Florida, specializing in clinical urology. The overall goal of this research partnership proposal is to design, engineer and evaluate in vivo a type I collagen-based bioactive nerve guide for peripheral nerve regeneration applications. The research team, through joint effort of the partnership, applies the current state-of-the- art knowledge of matrix technology, protein chemistry, neuroscience, neurosurgery and clinical urology to systematically evaluate the key design parameters. This systematic approach will lead to the development of a nerve guide that has the high probability of clinical success in nerve regeneration. The specific objectives of the proposal involve the isolation of the key design parameters and testing them in a rat sciatic nerve model. The final prototype, engineered from optimal design parameters, will be evaluated in two primate nerve models (median and cavernosal) as a potential entubulation repair method for clinical application. In the first year we will isolate the design parameters and engineer the prototypes. In subsequent years, we will characterize the prototypes, test in vivo performance of the prototypes in a rat model, finalize the overall design, and finally, evaluate the final prototype in primate models. The overall program is designed for five years.